Mayfield, who was the top overall pick of the 2018 NFL Draft, completed 27-of-37 passes for 284 yards and three touchdowns in the Browns' 26-18 victory over the Cincinnati Bengals on Sunday.
Philadelphia Eagles quarterback Nick Foles earned NFC Offensive Player of the Week honors after throwing for a franchise-record 471 yards and four touchdowns in Sunday's 32-30 win over the Houston Texans.
Baltimore Ravens linebacker Patrick Onwuasor was named the AFC Defensive Player of the Week after recording a team-high nine tackles and two sacks in Saturday's 22-10 triumph over the Los Angeles Chargers.
Los Angeles Rams defensive tackle Aaron Donald received NFC Defensive Player of the Week laurels following his three-sack, seven-tackle performance in Sunday's 31-9 romp over the Arizona Cardinals. His 19.5 sacks on the season are three shy of Michael Strahan's NFL record.
Oakland Raiders kick returner Dwayne Harris secured AFC Special Teams Player of the Week honors after returning a punt 99 yards for a touchdown in Monday's 27-14 victory versus the Denver Broncos. The punt return is tied for the second-longest in NFL history.